Cocaine abuse continues at an epidemic level with significant costs to society, yet no pharmacotherapy for cocaine abuse has demonstrated effectiveness for long-term use. The current project utilized a nonhuman primate model of drug self-administration to study the effectiveness of serotonin in altering the reinforcing and neurochemical effects of cocaine. The development and use of in vivo microdialysis to measure changes in brain chemistry in behaving monkeys represents a major advancement in our research efforts. Findings obtained and reported this year provide compelling evidence that serotonin can attenuate or block specific behavioral and neurochemical effects induced by cocaine, and that the 5HT2 receptor subtype may play a critical role in the observed interactions. These promising results suggest that the serotonin system is a potentially useful target in the pharmacological treatment of cocaine abuse.